Brain boost

Protein improves old rats’ ability to form new memories

Normal 0 false false false MicrosoftInternetExplorer4 You can teach an old rat new tricks, if you give him a shot of this stuff.

A form of gene therapy that boosted a protein in aged rats’ brains significantly improved the rats’ performance on memory tests, according to a new study.

The protein — called glial cell line-derived neurotrophic factor, or GDNF — holds promise as a way to relieve memory and motion control loss that comes with old age and with diseases such as Parkinson’s and Alzheimer’s, the researchers report in the September Neurobiology of Aging.

Previous GDNF trials on people with Parkinson’s disease suggested that direct injection of the protein into patients’ brains may have improved verbal memory and motion control. But the new study offers a clearer demonstration that the protein can partially restore age-related memory loss.

“This is a confirmation that this is a really useful molecule,” comments Steven Gill, a consultant neurosurgeon at FrenchayHospital in Bristol, England, who helped run the earlier human GDNF trial. “If we can master those — the neurotrophins, the delivery — then we can tackle these major neurodegenerative diseases.”

GDNF is normally produced in the brain by support cells that surround and nourish nerve cells. The protein stimulates nerve cells, causing them to thrive and to sprout new connections with neighboring neurons. These connections allow neurons to communicate and are believed to be crucial for how the brain stores new memories.

As rats and people reach old age, natural production of this protein appears to taper off, some research suggests. To give elderly but otherwise healthy rats’ brains a boost, a team led by Coral Sanfeliu of the Institute of Biomedical Research of Barcelona, in Spain, loaded a harmless virus with the gene that encodes GDNF. The researchers designed the virus to enter a specific kind of support cell in the brain, called an astrocyte, and insert the gene into the cell’s DNA. Then they injected the engineered virus directly into a memory-forming region of the brain called the hippocampus.

Two weeks after injection, the aged rats’ performance on a standard memory test improved by about 40 percent. That improvement closed half the performance gap between untreated elderly rats and young rats.

Placed in a small pool of water, the rats had to remember the location of a platform hidden just beneath the surface.

“As a proof of principle, it’s a great find,” comments Nik Patel, a consultant neurosurgeon and colleague of Gill’s at FrenchayHospital.

Using a virus to insert a gene into a person’s DNA is still a risky procedure, Patel cautions. “At the moment I certainly wouldn’t rely on it as fully safe, because there’s always the possibility of [tumors] over the long term.” That’s because inserting a gene can sometimes create cancer-causing mutations in the patient’s DNA.

Scientists are divided over whether viruses or direct injection through conventional catheters will be the more practical way to get GDNF into patients’ brains. But they agree that the protein could eventually provide a new way to treat age- and disease-related mental decline.

“Could this be the Botox of the brain?” Patel asks. “Who knows?”

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